In this paper, the theoretical simulation and experimental investigation are carried out on the gain coefficient process dependency of the advanced lithography focusing and leveling sensor. The theoretical model of gain coefficient process dependency was established to simulate and analyze the variations in the gain coefficient and measurement error of the focusing and leveling sensor with the film thickness of different materials for lithography process. The silicon wafers coated with SiO₂ films of different thicknesses were tested in our self-developed experimental system. The experimental results of variations in the gain coefficient and the measurement error with the film thickness are consistent with the theoretical simulation results. Simulation and experimental results show that the process dependency measurement error of the focusing and leveling sensor has the peak values about 55.9 nm and 36.6 nm at the SiO₂ film thicknesses of 250 nm and 690 nm, respectively. Using the silicon wafer coated with the specific film to calibrate the focusing and leveling sensor of the lithography machine can considerably reduce the effect of the gain coefficient process dependency and its measurement error. The investigation results of this paper can be used as reference to optimize the focusing control and lithography process.